Online Supplemental Information for:
A holistic approach identifies priority targets to reduce chronic diet-related
disease prevalence: an exhaustive review of pooled and meta-analyses
Anthony Fardet* and Yves Boirie
Affiliations:
A Fardet is with INRA, UMR 1019, UNH, CRNH Auvergne, F-63000 CLERMONTFERRAND & Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine,
BP 10448, F-63000 CLERMONT-FERRAND, France.
Y Boirie is with INRA, UMR 1019, UNH, CRNH Auvergne, F-63000 CLERMONTFERRAND, Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP
10448, F-63000 CLERMONT-FERRAND & CHU Clermont-Ferrand, Service de Nutrition
Clinique, F-63003 CLERMONT-FERRAND, France.
Correspondence: A Fardet, INRA, UMR 1019, UNH, CRNH Auvergne, F-63000 ClermontFerrand & Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP
10448, F-63000 Clermont-Ferrand, France. E-mail: anthony.fardet@clermont.inra.fr. Phone
: +33 (0)4 73 62 47 04. Fax: +33 (0)4 73 62 47 55.
Supporting Tables
Table S1. References that investigated the association between impaired physiological mechanisms and associated diet-related chronic diseases1
Antioxidant
status
Obesity or
overweight
→ 1-10
Lipid
metabolism
→ 11-14
Carbohydrate
metabolism
One-carbon
metabolism
Immune
system/Inflam
matory status
→ 15-19 14
↓ 27
→↓ 20, 40 15, 41-46
? 20, 21 22-26
? 28-32
? 47, 48
DNA
transcription/
Cell
proliferation
→ 49 50-57 58 59
Blood
pressure/flow
→ 14, 60-62
Nervous
system
Acido-basic
status
→↓ 63-72
→ 73-75
 72
? 6, 76
→ 70, 93, 142-157
→ 161-166
Digestive
microflora
→↓ 47, 64, 77-91 92
 10, 33-39
Diabetes
→↓ 1, 93-100 101
→↓ 11, 12, 107-109
102, 103 104 9, 105,
106
→↓ 20, 110-115
→ 117-122
→↓ 20, 125-127
→ 130 131 132-136
→↓ 138-141
 116
 103, 123, 124
 128, 129
 137
 142
→↓ 188-192
↓ 193-197
→↓ 199-208
↓ 210-220
→↓ 222-229
158, 159 160
170 171
 167 170
 94
Mental diseases
→↓ 172-179
 180
Skeleton diseases
↓ 308-321
→↓ 181-185
 185-187
↓ 322, 323 321, 324330

Sarcopenia
Digestive diseases
↓ 394-398
→↓ 93, 446-457
 458
 188, 190, 192
↓ 323, 333 334-344
 344, 345
331, 332
↓ 317, 346, 347 348
→↓ 399, 402-407
 401
 401, 408, 409
→↓ 56, 459-463
→↓ 42, 467 468 56,
 209
↓ 356 323, 357, 358
 221
 187, 223, 230
→↓ 231-240 241,
119
↓ 395-397, 410-421

→ 472 473-478
469-471
? 294-300

↓ 327, 367-375
? 365
? 332, 375, 376
 366
 371
↓ 395, 396, 423-430
↓ 431
↓ 432-435
 401
? 430
→↓ 514-529
→↓ 530 531-534
↓ 479 480-492 493
→↓ 501, 502 503-
494-499
513
↓ 377-379
 528
 492, 496, 500
↓ 301 302-307
273, 281, 290
↓ 359-364
? 422
↓ 291-293
242 207, 243-289
349-355
?
→↓ 399, 400
 464-466
 197, 198
? 81, 82, 85, 167-169
↓ 380-387
↓ 389-392
 388
 393
↓ 381, 384, 436-445

→↓ 535 536-539
→↓ 541-543 544-
 540 537
564
 548, 553, 560, 565567
Liver diseases
→↓ 568 569-573
 568, 574
→↓ 11, 12, 574, 575
 574
→↓ 576 574, 577,
→↓ 579-582 583-
578
587

574, 577

→↓ 12, 574, 589-592
 574, 591
588
→↓ 593-596 597
→↓ 605, 606 574
598-602
375, 607-616


596, 603 604
606 574
→ 617-624
→ 625-636
↓ 301 90, 637-652
 653
Kidney diseases
→ 96, 654-661
→↓ 662-664 665-
→↓ 664 166, 676-
→↓ 686-690 691,
→↓ 705 658, 661,
670 671 672-675
685
692 693-696 697 119,
666, 676, 706-710

Cardiovascular
diseases
 726
698-704
↓ 771 662, 772-801
↓ 20, 791, 803, 825,
802 140, 803-838
844-860


775, 778, 780, 783,
785, 797, 811, 818,
825, 849, 851, 852,
↓ 865-882
 691, 868, 872, 883,
884
↓ 885, 886 20, 208,
↓ 906 907-911
803, 887-901
→↓ 997 998-1002
 998, 1002, 1003
→↓ 162, 381, 386,
→↓ 463, 1004-1015
 796, 811, 823, 1016
↓ 753-755
681, 751, 752
? 746, 756, 757
? 912, 913

↓ 771 138, 140, 789,
→↓ 963 70, 964-980
825, 841, 914-959
→↓ 981-992
↓ 994, 995
 993
 996
→↓ 1117-1124
↓ 555, 561, 1125-1142
902-905
 138, 803, 840, 924,
859, 861-864
955, 956, 960-962
→↓ 1004, 1017 1018
18, 56, 463, 1019-1031

1032, 1033 1029,
1034
1
 735
791, 793, 803, 807,
825-827, 831, 839-843
Cancers
→↓ 70, 727-750
 758
763, 764 765 766 767,
 762, 765, 768 770
→↓ 664, 720-725
662, 671
↓ 759 760 761 762
768 769
→↓ 711 712-719
↓ 1035, 1036
 1035-1038
↓ 1039, 1040 997,
↓ 1056-1068 997
↓ 516, 1034, 1098,
1041 705, 1042-1053
1042, 1069-1089
1099 722 1020, 1024,


1041 1039, 1040,
1100-1107
→↓ 1110-1116
 1113
 1126, 1131, 1134,
1139, 1143
1045, 1068-1070,
1043, 1044, 1050,
1090-1094 604 1074,

1052, 1054, 1055
1083, 1095-1097
1104, 1109
1034, 1108 944
References were chosen as follows: meta/pooled analyses and systematic reviews were selected first, then observational and intervention studies and/or classic reviews; in some cases, it was not possible to differentiate a meta-analysis from a
pooled analysis stricto sensu based on methodological description given in the paper: thus, both analyses were confounded; when at least two meta/pooled/quantitative analyses were found, other studies were included only when
meta/pooled/quantitative analyses or systematic review(s) were too ancient, not sufficiently convincing or were not sufficiently reflecting the range of potential associations: for example, mental health disorders cover a wide range of diseases and
only 3 meta-analyses may not reflect all mental pathologies; the same is true for cancers that affect several types of organs; otherwise when possible, abstract articles from congresses were avoided; human case reports, animal studies and in vitro
studies were not included, except when they were cited in classic reviews; colour codes are as follows: pooled and meta-analyses are in grey, systematic reviews in blue and other studies (classic reviews and observational and interventional
studies) in white
→ Pathology may be causal or triggering factor for impaired physiological mechanism
↓ Impaired metabolism pathway or physiological mechanism may be causal or triggering factor for pathology development
→↓ Both pathology and impaired metabolism pathway or physiological mechanism may be causal or triggering factors
? Pathology and impaired metabolism pathway or physiological mechanism are associated, but with no indication for the direction of causality or association
 Pathology and impaired metabolism/physiological mechanism are not significantly associated
 No reference was found for the association between the impaired metabolism pathway or physiological mechanism and the pathology considered
Table S2. Association between main chronic diseases1
Diabetes
Obesity or
overweight
→ 60, 807, 11441149
Mental
diseases
→↓ 1150-1156
 1156
Skeleton diseases
Sarcopenia
Digestive tract
diseases
Cancers
Cardiovascular
diseases
→ 1157 60, 1158
→↓ 415, 418, 1164-
→↓ 1172 40, 58,
→ 60, 1173, 1174,
→ 771 60, 807, 812,
1159, 1160 1161
1171
1173-1177
1178-1218
841, 940, 1221-1233
 1162, 1163
 401
 60, 1196, 1200,
 60, 825, 840, 1186,
1202, 1206, 1208,
1224, 1234
Liver diseases
→ 11, 12, 1235
Kidney diseases
→ 664, 1197, 1199,
1236, 1237
1210, 1218-1220
Diabetes
→↓ 187, 189, 227,
→ 1252 333 372,
1151, 1238-1243
1252-1257 339 343,
1244 1245-1247
1258-1263
1248 1249-1251
 1240, 1247
Mental
diseases
 1253, 1259
→ 1310-1314
 1315-1318
→ 406, 1264-1267
→↓ 127, 1269,
→↓ 131, 1195,
→ 771 789, 791, 803,
→↓ 11, 12, 1235,
1270
1275-1295
812, 841, 845, 1297-1303
1280, 1284, 1304,


? 409, 1268
 403, 409
1271 1269 1272-
1305
1032, 1296
→↓ 534, 1325-1329
1319-1323
1330
 417, 1268, 1324
 227, 1331
→↓ 1332-1336
 227, 1331, 13371340
? 1307
 1308, 1309
1274
→↓ 421, 1317,
→ 1282 687, 1306 1270
→↓ 771, 1341 227,
245, 1250, 1342-1358
 1331 1359 1351,
↓ 623, 1360-1364
 1331
→↓ 727, 1306, 13651372 227 1373-1385
 1331 1372
1355, 1357
Skeleton
diseases
? 1386-1392 422
↓ 1398-1413 1414
→↓ 1425 1426,
1393 1394-1396
1415-1420 1421
1427 1428 360,
1422-1424
1429-1435
 1324, 1397
Sarcopenia
→↓ 891, 894, 897
↓ 1436-1443
↓ 367, 388, 1441, 1442,
1444-1446
 1432, 1434
↓ 1394, 1396, 1403,
↓ 1449-1451
↓ 1268, 1452-1458
↓ 1459-1462
↓ 1463 438, 1464-1466
→ 502, 1467-1475
→↓ 1478 899, 994,
↓ 1486, 1487 1488
→↓ 1307, 1502-1505
996, 1476, 1479-1484
1489 1490 1491
1506 1501, 1507-1511
1413, 1415, 1447,
1448
Digestive tract
diseases
 501, 1467, 1469,
1471, 1472, 1476,
 1468, 1476, 1485
1476 1492 522,
1493-1498
 1501
1477
? 1499
 1500, 1501
Cancers
→↓ 1512 1513-1515
1516

1517
→↓ 1518-1525
→↓ 719, 1526-1537
 1528 1538
Cardiovascular
diseases
↓ 1539-1545
→↓ 1547-1552 1553,
1554 1555-1559
? 1546
Liver diseases
→↓ 1307, 1539, 1560
1561, 1562 1563 1564,
1565
 1566
Kidney diseases
1
References were chosen as follows: meta/pooled analyses and systematic reviews were selected first, then observational and intervention studies and/or classic reviews; in some cases, it was not possible to differentiate a
meta-analysis from a pooled analysis stricto sensu based on methodological description given in the paper: thus, both analyses were confounded; when at least two meta/pooled/quantitative analyses were found, other studies
were included only when meta/pooled/quantitative analyses or systematic review(s) were too ancient, not sufficiently convincing or were not sufficiently reflecting the range of potential associations: for example, mental
health disorders cover a wide range of diseases and only 3 meta-analyses may not reflect all mental pathologies; the same is true for cancers that affect several types of organs; otherwise when possible, abstract articles from
congresses were avoided; human case reports, animal studies and in vitro studies were not included, except when they were cited in classic reviews; colour codes are as follows: pooled and meta-analyses are in grey,
systematic reviews in blue and other studies (classic reviews and observational and interventional studies) in white
→ Indicates that pathology in the row may be risk factor for pathology in the column
↓ Indicates that pathology in the column may be risk factor for pathology in the row
→↓ Indicates that both pathologies may be risk factor for each other
? Indicates that pathologies are associated with no indication of which one may be risk factor for the other one
 Indicates that pathologies are not significantly associated
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28
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33
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35
36
37
38
39
40
41
42
43
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47
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49
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